Patients With Aldolase B Deficiency Are Characterized by Increased Intrahepatic Triglyceride Content.

Area of Science:

• Metabolic disorders
• Hepatology
• Genetics

Background:

• Nonalcoholic fatty liver disease (NAFLD) pathogenesis is debated, with fructose metabolism a potential factor.
• Experimental studies in mice showed increased intrahepatic triglyceride (IHTG) in aldolase B deficient models.
• Aldolase B is crucial for fructose metabolism, converting fructose-1-phosphate to triose phosphates.

Purpose of the Study:

• To investigate the role of aldolase B deficiency in human IHTG accumulation.
• To translate experimental findings on fructose metabolism and NAFLD to a human context.
• To explore the relationship between aldolase B defect, fructose metabolism, and liver fat accumulation in humans.

Main Methods:

• Case-control study comparing patients with hereditary fructose intolerance (aldolase B deficiency) to healthy controls.
• Intrahepatic triglyceride (IHTG) content assessed using proton magnetic resonance spectroscopy.
• Evaluated glucose excursions and measured hypoglycosylated transferrin and plasma β-hydroxybutyrate levels.

Main Results:

• Aldolase B deficient patients exhibited significantly higher IHTG content (2.5% vs 0.6%) compared to controls.
• Increased glucose excursions and higher abundance of hypoglycosylated transferrin were observed in patients.
• Lower plasma β-hydroxybutyrate levels indicated impaired hepatic β-oxidation in aldolase B deficient individuals.

Conclusions:

• Human aldolase B deficiency is associated with intrahepatic triglyceride accumulation.
• Fructose-1-phosphate accumulation and impaired beta-oxidation are implicated in the pathogenesis of liver fat accumulation.
• Findings support a role for fructose metabolism dysregulation in nonalcoholic fatty liver disease.